Formation of Cubic Phases from Large Unilamellar Vesicles of Dioleoylphosphatidylglycerol/Monoolein Membranes Induced by Low Concentrations of Ca2

We developed a new method for the transformation of large unilamellar vesicles (LUVs) into the cubic phase. We found that the addition of low concentrations of Ca2+ to suspensions of multilamellar vesicles (MLVs) of membranes of monoolein (MO) and dioleoylphosphatidylglycerol (DOPG) mixtures (DOPG/MO) changed their Lα phase to the cubic phases. For instance, the addition of 15−25 mM Ca2+ to 30%-DOPG/70%-MO-MLVs induced the Q229 phase, whereas the addition of ≥28 mM Ca2+ induced the Q224 phase. LUVs of DOPG/MO membranes containing ≥25 mol % DOPG were prepared easily. Low concentrations of Ca2+ transformed these LUVs in excess buffer into the Q224 or the Q229 phase, depending on the Ca2+ concentration. For example, 15 and 50 mM Ca2+ induced the Q224 and Q229 phase in the 30%-DOPG/70%-MO-LUVs at 25 °C, respectively. This finding is the first demonstration of transformation of LUVs of lipid membranes into the cubic phase under excess water condition.